Synthesis and structure-activity relationship studies of 1,3-disubstituted 2-propanols as BACE-1 inhibitors |
| |
Authors: | Kumar Arun Babu Anderson Jordan Micheal Melendez Anthony Lester Manetsch Roman |
| |
Institution: | Department of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Ave, Tampa, FL 33620, USA. |
| |
Abstract: | A library of 1,3-disubstituted 2-propanols was synthesized and evaluated as low molecular weight probes for β-secretase inhibition. By screening a library of 121 1,3-disubstituted 2-propanol derivatives, we identified few compounds inhibiting the enzyme at low micromolar concentrations. The initial hits were optimized to yield a potent BACE-1 inhibitor exhibiting an IC(50) constant in the nanomolar range. Exploration of the pharmacological properties revealed that these small molecular inhibitors possessed a high selectivity over cathepsin D and desirable physicochemical properties beneficial to cross the blood-brain barrier. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|